WS07.06Early change in forced vital capacity as a determinant of outcome in pulmonary exacerbations of cystic fibrosis

Objectives

To characterize the impact of acute pulmonary exacerbations (PEx) of CF on forced vital capacity (FVC, both absolute volume and percent of predicted), identify differences in FVC trajectory among exacerbating PwCF and clarify the association between FVC phenotypes and clinical outcomes.

Methods

We performed a secondary analysis of STOP2, a large randomized trial of antimicrobial treatment durations for PEx, that measured FVC at scheduled intervals (n=854). Patterns of FVC decline and trajectory of FVC response were evaluated, and multivariate logistic regression used to identify factors associated with pronounced loss of FVC, as well as with early FVC responses to antibiotics. Differences in absolute FVC recovery, residual FVC loss, symptomatic improvement, and time to next PEx by FVC phenotype were assessed among matched participants. The performance of FVC as a PEx endpoint was investigated via comparison with FEV₁.

Results

PEx-induced FVC loss varied within the cohort. Large FVC decreases were associated with Pseudomonas aeruginosa in sputum, circulating C-reactive protein (CRP) concentration ≥30mg/L and age <30, and negatively associated with CFTR modulator use. Although participants with large FVC decreases recovered greater absolute volumes than those with smaller FVC decreases, their residual FVC deficit remained greater. An early FVC response was associated with large initial FVC loss, male sex, age <30, and CRP <30mg/L. Early FVC responders had more complete resolution to baseline FVC and greater symptomatic improvement compared to matched controls. For the overall cohort, the effects of antibiotic duration on FVC and FEV₁ were similar, however with larger variance FVC may be a less sensitive trial measure in certain populations.

Conclusions

Distinct FVC decline and FVC response phenotypes exist in acute CF PEx and are associated with differential clinical outcomes. The added utility of FVC as a clinical trial endpoint in PEx is uncertain.